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Antonio Cardesa · Pieter J. Slootweg (Eds.) Pathology of the Head and Neck Antonio Cardesa · Pieter J. Slootweg (Eds.)

Pathology of the Head and Neck

With 249 Figures in 308 separate Illustrations and 17 Tables

123 Professor Dr. Antonio Cardesa Department of Pathological Anatomy Hospital Clinic University of Barcelona Villarroel 170 08036 Barcelona Spain

Professor Pieter J. Slootweg Department of Pathology University Medical Center St. Radboud P.O. Box 9101 6500 HB Nijmegen The Netherlands

Library of Congress Control Number: 2006922731

ISBN-10 3-540-30628-5 Springer Berlin Heidelberg New York ISBN-13 978-3-540-30628-3 Springer Berlin Heidelberg New York

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfi lms or in any other way and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under German Copyright Law.

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Editor: Gabriele Schröder, Heidelberg Desk Editor: Ellen Blasig, Heidelberg Production: LE-TEX, Jelonek, Schmidt & Vöckler GbR, Leipzig Typesetting: Satz-Druck-Service, Leimen Cover: Frido Steinen-Broo, eStudio Calamar, Spain Printed on acid-free paper 24/3100/YL 5 4 3 2 1 0 To Gerhard Seifert and to Leslie Michaels, great pioneers of Head and Neck Pathology in Europe and founding members of the Working Group on Head and Neck Pathology of the European Society of Pathology. Foreword

Pathology of the Head and Neck is an easy sounding pathology of the head and neck that remain an unex- title for a complex subject matter. This title stands for an plored world. Examples include the never-ending prob- accumulation of diverse diseases occurring in different lem of prognostication of tumour diseases, the patho- organs whose relationship to each other consists in the genetic significance of tumour precursor lesions and fact that they are located between the base of the skull the validation of appropriate sets of tumour markers as and the thoracic aperture. One reason for assembling meaningful predictors of malignancy. all these different organs under the title “Pathology of The editors of the book, Professor Antonio Carde- the Head and Neck” is that the proximity of the organs sa and Professor Pieter Slootweg, are leading experts in of the head and neck region makes it difficult for the the field of the pathology of the head and neck. As such surgical pathologist to focus on one of these organs and they are the main members of the Working Group on neglect the pathology of others, which are only a centi- Pathology of the Head and Neck of the European Society metre apart. A second reason, however, is that the upper of Pathology, one of the first European working groups digestive tract and the upper respiratory tract, which to be founded under the auspices of the European Soci- meet in the larynx, have some basic diseases in com- ety of Pathology. In this multi-author book the exper- mon, notably squamous cell carcinoma. Thus pathology tise of outstanding experts on the pathology of the head of the head and neck is both an arbitrary compilation of and neck in Europe is reflected. The chapters are char- diseases and, at least to some extent, a group of disease acterised by the desire to correlate pathology with all entities with a common morphological and pathoge- necessary information on clinical features, epidemiolo- netic trunk. gy, pathogenesis and molecular genetics. The authors of The past years have seen remarkable advances in these chapters have not attempted to be encyclopaedic, many fields of pathology, including that of the head and but rather have aimed at providing concise, yet adequate neck. There is a need for a book that integrates surgical knowledge. They are therefore to be warmly commend- pathology with molecular genetics, epidemiology, clin- ed for providing us with an excellent book, which will ical behaviour and biology. This book provides a com- prove useful to surgical pathologists involved in the pa- prehensive description of the manifold aspects of the thology of the head and neck. morphology and pathology of the organs of the head and neck region. These description, as comprehensive as Kiel, Germany Günter Klöppel they may be, also show that there are some areas of the March 2006 Contents IX

Preface

This book was initially conceived as a unitary group of adnexa. The pathology of the thyroid and parathyroid chapters on “Pathology of the Head and Neck”, to be glands and lymph nodes is covered in greater detail published in German within the series of volumes of elsewhere. Remmele’s Textbook of Pathology. From the outset, the Since the authors selected for writing the different editorial approach was to concentrate on pathological chapters are international experts and members of the entities that are either unique to or quite characteristic of Working Group on Head and Neck Pathology of the the head and neck. At the same time, we strove to avoid European Society of Pathology, the chief editors of the as much as possible unnecessary details on systemic series, Prof. Wolfgang Remmele, Prof. Hans Kreipe and diseases that, although involving the head and neck Prof. Günter Klöppel, accepted that all manuscripts region, have their main focus of activity in other organs. should be in English. After the original texts had been Thus, “Pathology of the Head and Neck” encompasses submitted, it became clear to the editors and publisher the wide range of diseases encountered in the complex that, in addition to their translation to fit into Remme- anatomic region extending proximally from the frontal le’s Textbook, the work warranted publication in English sinuses, orbits, roof of the sphenoidal sinuses and clivus as a separate book. Therefore, we want to thank the chief to distally the upper borders of the sternal manubrium, editors and the publisher Springer for their stimulating clavicles and first ribs. This includes the eyes, ears , upper support and trust. We add our special thanks to the au- aerodigestive tract, salivary glands, dental apparatus, thors who produced such an excellent work, as well as to thyroid and parathyroid glands, as well as all the those secretaries, photographers and others who helped epithelial, fibrous, fatty, muscular, vascular, lymphoid, them. cartilaginous, osseous and neural tissues or structures Finally, we should like to express our wish that this related to them. book on “Pathology of the Head and Neck”, the first The contents have been divided into ten chapters. The ever written as a joint project by a Working Group of the first covers the spectrum of precursor and neoplastic European Society of Pathology, could serve as an example lesions of the squamous epithelium. It is followed by for new books written by other Working Groups. chapters devoted to the nasal cavities and paranasal sinuses, oral cavity, maxillofacial skeleton and teeth, Barcelona, Spain Prof. Antonio Cardesa salivary glands, nasopharynx and Waldeyer`s ring, larynx and hypopharynx, ear and temporal bone, Nijmegen, The Netherlands Prof. Pieter J. Slootweg neck and neck dissection, as well as eye and ocular March 2006 Contents

1 Benign and Potentially Malignant 1.3.2.4 Invasive Front ...... 15 Lesions of the Squamous Epithelium 1.3.2.5 Stromal Reaction ...... 15 and Squamous Cell Carcinoma . . . . 1 N. Gale, N. Zidar 1.3.2.6 Diff erential Diagnosis ...... 15 1.3.2.7 Treatment and Prognosis ...... 15 1.1 Squamous Cell 1.3.3 Spindle Cell Carcinoma ...... 16 and Related Lesions ...... 2 1.3.3.1 Aetiology ...... 16 1.1.1 Squamous Cell Papilloma, Verruca Vulgaris, 1.3.3.2 Pathologic Features ...... 16 Condyloma Acuminatum 1.3.3.3 Diff erential Diagnosis ...... 17 and Focal Epithelial Hyperplasia . . . . . 2 1.3.3.4 Treatment and Prognosis ...... 17 1.1.2 Laryngeal Papillomatosis ...... 3 1.3.4 ...... 17 1.3.4.1 Aetiology ...... 17 1.2 Squamous Intraepithelial Lesions (SILS) 4 1.3.4.2 Pathologic Features ...... 18 1.2.1 General Considerations ...... 4 1.3.4.3 Diff erential Diagnosis ...... 18 1.2.2 Terminological Problems ...... 4 1.3.4.4 Treatment ...... 18 1.2.3 Aetiology ...... 5 1.3.4.5 Prognosis ...... 19 1.2.3.1 Oral Cavity and Oropharyn ...... 5 1.3.5 Papillary Squamous Cell Carcinoma . . . . 19 1.2.3.2 Larynx ...... 5 1.3.5.1 Aetiology ...... 19 1.2.4 Clinical Features 1.3.5.2 Pathologic Features ...... 19 and Macroscopic Appearances ...... 6 1.3.5.3 Diff erential Diagnosis ...... 20 1.2.4.1 Oral and Oropharyngeal , 1.3.5.4 Treatment and Prognosis ...... 20 Proliferative Verrucous Leukoplakia 1.3.6 Basaloid Squamous Cell Carcinoma . . . . 20 and ...... 6 1.3.6.1 Aetiology ...... 20 1.2.4.2 Laryngeal and Hypopharyngeal 1.3.6.2 Pathologic Features ...... 20 Leukoplakia and Chronic Laryngitis . . . 7 1.3.6.3 Diff erential Diagnosis ...... 21 1.2.5 Histological Classifi cations ...... 8 1.3.6.4 Treatment and Prognosis ...... 21 1.2.5.1 WHO Dysplasia System ...... 8 1.3.7 Adenoid Squamous Cell Carcinoma . . . . 22 1.2.5.2 Th e Ljubljana Classifi cation ...... 9 1.3.7.1 Pathologic Features ...... 22 1.2.5.3 Comparison Between 1.3.7.2 Diff erential Diagnosis ...... 22 the Ljubljana Classifi cation 1.3.7.3 Treatment and Prognosis ...... 22 and WHO 2005 Classifi cation ...... 11 1.3.8 Adenosquamous Carcinoma ...... 23 1.2.6 Biomarkers Related to Malignant Potential 1.3.8.1 Aetiology ...... 23 of SILs Recognised by Auxiliary 1.3.8.2 Pathologic Features ...... 23 and Advanced Molecular Methods . . . . . 12 1.3.8.3 Diff erential Diagnosis ...... 23 1.2.7 Treatment and Prognosis ...... 12 1.3.8.4 Treatment and Prognosis ...... 24 1.2.7.1 Oral Cavity and Oropharynx ...... 12 1.3.9 Lymphoepithelial Carcinoma ...... 24 1.2.7.2 Larynx ...... 13 1.3.9.1 Aetiology ...... 24 1.3 Invasive Squamous Cell Carcinoma . . . . 13 1.3.9.2 Pathologic Features ...... 24 1.3.1 Microinvasive Squamous 1.3.9.3 Diff erential Diagnosis ...... 25 Cell Carcinoma ...... 13 1.3.9.4 Treatment and Prognosis ...... 25 1.3.2 Conventional Squamous 1.4 Second Primary Tumours ...... 25 Cell Carcinoma ...... 13 1.3.2.1 Aetiology ...... 14 1.5 Tumour Spread and Metastasising . . . . 25 1.3.2.2 Pathologic Features ...... 14 1.5.1 Invasion of Lymphatic 1.3.2.3 Grading ...... 14 and Blood Vessels ...... 26 XII Contents

1.5.2 Perineural Invasion ...... 26 2.6.2 Mucormycosis ...... 44 1.5.3 Regional Metastases . . . . . 26 2.6.3 Rhinosporidiosis ...... 44 1.5.3.1 Extracapsular Spread 2.7 HIV-Related Infections ...... 44 in Lymph Node Metastases ...... 26 1.5.3.2 Metastases in the Soft Tissue 2.8 Mid-Facial Necrotising of the Neck ...... 27 Granulomatous Lesions ...... 45 1.5.4 Distant Metastasis ...... 27 2.8.1 Wegener’s Granulomatosis ...... 45 1.5.5 Micrometastasis ...... 27 2.8.2 Lepromatous Leprosy ...... 45 2.8.3 ...... 45 1.6 Molecular Pathology 2.8.4 ...... 45 of Squamous Cell Carcinoma ...... 28 2.8.5 Rhinoscleroma ...... 45 1.6.1 Detecting Tumour Cells ...... 28 2.8.6 Leishmaniasis ...... 45 1.6.2 Clonal Analysis ...... 28 2.8.7 Cocaine Abuse ...... 46 1.6.3 Assessment of Risk 2.8.8 Local Steroid Injections ...... 46 for Malignant Progression ...... 29 1.6.4 DNA/RNA Profi ling 2.9 Benign Epithelial Neoplasms ...... 46 in Predicting Metastatic Disease ...... 29 2.9.1 Sinonasal ...... 46 2.9.1.1 Squamous Cell Papilloma ...... 46 References ...... 29 2.9.1.2 Exophytic Papilloma ...... 46 2 Nasal Cavity 2.9.1.3 ...... 46 2.9.1.4 Oncocytic Papilloma ...... 47 and Paranasal Sinuses ...... 39 A. Cardesa, L. Alos 2.9.2 Salivary-Type Adenomas ...... 48 2.9.3 Pituitary Adenomas ...... 48 2.1 Introduction ...... 40 2.10 Benign Sinonasal 2.1.1 Embryology ...... 40 Soft Tissue Neoplasms ...... 48 2.1.2 Anatomy ...... 40 2.10.1 Haemangiomas ...... 48 2.1.3 Histology ...... 40 2.10.2 Haemangiopericytoma ...... 48 2.2. Acute and Chronic Rhinosinusitis . . . . . 40 2.10.3 Solitary Fibrous Tumour ...... 48 2.2.1 Viral Infections (Common Cold) ...... 40 2.10.4 Desmoid Fibromatosis ...... 49 2.2.2 Bacterial Infections ...... 40 2.10.5 Fibrous Histiocytoma ...... 49 2.2.3 Allergic Rhinitis ...... 40 2.10.6 Leiomyoma ...... 49 2.2.4 Atrophic Rhinitis ...... 41 2.10.7 Schwannoma and Neurofi broma ...... 49 2.2.5 Hypertrophic Rhinitis ...... 41 2.10.8 Meningioma ...... 50 2.2.6 Non-Suppurative Chronic Sinusitis . . . . 41 2.10.9 Paraganglioma ...... 50 2.10.10 Juvenile Angiofi broma ...... 50 2.3 Sinonasal Polyps ...... 41 2.3.1 Allergic Polyposis ...... 41 2.11 Malignant Sinonasal Tumours ...... 50 2.3.2 Polyposis in Mucoviscidosis ...... 41 2.11.1 Keratinising Squamous 2.3.3 Polyposis in Immotile Cilia Syndrome Cell Carcinoma ...... 51 and in Kartagener’s Syndrome ...... 41 2.11.2 Cylindrical Cell Carcinoma ...... 52 2.3.4 Antrochoanal Polyps ...... 41 2.11.3 Sinonasal Undiff erentiated Carcinoma ...... 53 2.4 Sinonasal Hamartomatous 2.11.4 Small Cell (Neuroendocrine) and Teratoid Lesions ...... 42 Carcinoma ...... 54 2.4.1 Hamartomas ...... 42 2.11.5 Primary Sinonasal 2.4.2 Teratoid Lesions ...... 42 Nasopharyngeal-Type 2.5 Pseudotumours ...... 43 Undiff erentiated Carcinoma ...... 54 2.5.1 Mucocele ...... 43 2.11.6 Malignant Melanoma ...... 55 2.5.2 Organising Haematoma ...... 43 2.11.7 Olfactory Neuroblastoma ...... 57 2.5.3 Amyloidosis ...... 43 2.11.8 Primitive Neuroectodermal Tumour . . . . 58 2.5.4 Myospherulosis ...... 43 2.11.9 High-Grade Sinonasal 2.5.5 Eosinophilic Angiocentric Fibrosis . . . . 43 ...... 58 2.5.6 Heterotopic Brain Tissue ...... 43 2.11.9.1 Intestinal-Type ...... 58 2.6 Fungal Diseases ...... 44 2.11.9.2 Salivary-Type High-Grade 2.6.1 Aspergillosis ...... 44 Adenocarcinoma ...... 60 Contents XIII

2.11.10 Low-Grade Sinonasal 3.4.7 Hairy Tongue ...... 85 Adenocarcinomas ...... 60 3.4.8 ...... 85 2.11.10.1 Non-Salivary-Type 3.4.9 ...... 85 Low-Grade Adenocarcinomas ...... 60 3.4.10 Frictional Keratosis ...... 86 2.11.10.2 Salivary-Type 3.5 Pigmentations ...... 86 Low-Grade Adenocarcinomas ...... 61 3.5.1 ...... 86 2.11.11 Sinonasal Malignant . . . . . 61 3.5.2 Localised Melanotic Pigmentation . . . . 86 2.11.12 Extramedullary Plasmacytoma ...... 62 3.5.2.1 Oral Melanotic Macules ...... 86 2.11.13 Fibrosarcoma ...... 62 3.5.2.2 Melanoacanthoma ...... 87 2.11.14 Malignant Fibrous Histiocytoma . . . . . 63 3.5.2.3 Pigmented Naevi ...... 87 2.11.15 Leiomyosarcoma ...... 63 3.5.3 Premalignant Oral Melanoses 2.11.16 Rhabdomyosarcoma ...... 63 and Oral Melanoma ...... 87 2.11.17 Malignant Peripheral 3.5.4 Addison Disease ...... 88 Nerve Sheath Tumour ...... 63 3.5.5 Peutz Jeghers Syndrome ...... 89 2.11.18 Teratocarcinosarcoma ...... 63 3.5.6 Racial Pigmentation ...... 89 References ...... 64 3.5.7 Laugier Hunziker Syndrome ...... 89 3.5.8 Smoker’s Melanosis ...... 89 3 Oral Cavity ...... 72 3.5.9 Drug-Associated J.W. Eveson ...... 90 3.1 Embryonic Rests and Heterotopias . . . . 72 3.6 Hyperplastic Lesions ...... 90 3.1.1 Fordyce Granules/Spots ...... 72 3.6.1 Fibrous Hyperplasias ...... 90 3.1.2 Juxtaoral Organ of Chievitz ...... 72 3.6.2 Papillary Hyperplasia ...... 90 3.6.3 Generalised Gingival 3.2. Vesiculo-Bullous Diseases ...... 72 Fibrous Hyperplasia ...... 91 3.2.1 Infections ...... 72 3.6.4 Crohn’s Disease ...... 91 3.2.2 Chickenpox and Herpes Zoster ...... 73 3.6.5 ...... 92 3.2.3 Hand-Foot-and-Mouth Disease ...... 73 3.6.6 Chronic Marginal 3.2.4 ...... 74 and Localised Gingival 3.2.5 Vulgaris ...... 74 Fibrous Hyperplasia ...... 92 3.2.6 Pemphigus Vegetans ...... 74 3.6.7 Peripheral Giant Cell 3.2.7 Paraneoplastic Pemphigus ...... 75 (Giant Cell ) ...... 93 3.2.8 ...... 75 3.6.8 ...... 93 3.2.9 Herpetiformis ...... 76 3.6.9 Pulse (Vegetable) Granuloma ...... 93 3.2.10 Linear IgA Disease ...... 76 3.2.11 Multiforme ...... 77 3.7 Benign Tumours and Pseudotumours ...... 94 3.3 Ulcerative Lesions ...... 77 3.7.1 Giant Cell ...... 94 3.3.1 Aphthous 3.7.2 Lingual Th yroid ...... 94 (Recurrent Aphthous Ulceration) . . . . . 77 3.7.3 ...... 95 3.3.2 Behçet Disease ...... 78 3.7.4 Haemangiomas ...... 95 3.3.3 Reiter Disease ...... 78 3.7.5 Lymphangioma ...... 95 3.3.4 Median Rhomboid ...... 78 3.7.6 Benign Nerve Sheath Tumours ...... 95 3.3.5 Eosinophilic Ulcer 3.7.6.1 Neurofi broma ...... 96 (Traumatic Ulcerative Granuloma 3.7.6.2 Schwannoma ...... 96 with Stromal Eosinophilia) ...... 79 3.7.6.3 Neurofi bromatosis ...... 96 3.3.6 Acute Necrotising 3.7.6.4 Multiple Neuromas Ulcerative Gingivitis ...... 79 in Endocrine Neoplasia Syndrome . . . . 96 3.3.7 Wegener’s Granulomatosis ...... 80 3.7.7 Granular Cell Tumour 3.3.8 Tuberculosis ...... 81 (Granular Cell Myoblastoma) ...... 96 3.4 White Lesions ...... 81 3.8 Squamous Cell Carcinoma ...... 96 3.4.1 Candidosis ...... 81 3.8.1 Introduction ...... 96 3.4.2 ...... 82 3.8.2 Clinical Features ...... 97 3.4.3 ...... 83 3.8.2.1 Buccal Mucosa ...... 97 3.4.4 Oral Epithelial Naevi ...... 84 3.8.2.2 Tongue ...... 97 3.4.5 Smoker’s Keratosis ...... 84 3.8.2.3 Floor of Mouth ...... 97 3.4.6 ...... 84 XIV Contents

3.8.2.4 Gingiva and Alveolar Ridge ...... 97 4.4.3.6 Calcifying ...... 118 3.8.2.5 Hard ...... 98 4.4.4 Odontogenic Tumours – 3.8.2.6 Retromolar Trigone ...... 98 Malignant ...... 119 3.8.3 Staging ...... 98 4.4.4.1 Malignant Ameloblastoma ...... 119 4.4.4.2 Ameloblastic Carcinoma ...... 119 References ...... 98 4.4.4.3 Primary Intraosseous Carcinoma . . . . 119 4.4.4.4 Clear Cell Odontogenic Carcinoma . . . 120 4 Maxillofacial Skeleton 4.4.4.5 Malignant Epithelial Odontogenic and Teeth ...... 104 P.J. Slootweg Ghost Cell Tumour ...... 120 4.4.4.6 Odontogenic Sarcoma ...... 120 4.1 Introduction ...... 104 4.5 Fibro-Osseous Lesions ...... 121 4.1.1 Embryology ...... 104 4.5.1 Fibrous Dysplasia ...... 121 4.1.2 Tooth Development ...... 104 4.5.2 Ossifying Fibroma ...... 121 4.2 Infl ammatory Diseases 4.5.3 Osseous Dysplasia ...... 123 of the Maxillofacial Bones ...... 104 4.6 Giant Cell Lesions ...... 124 4.3 ...... 105 4.6.1 Central Giant Cell Granuloma ...... 124 4.3.1 Odontogenic Cysts – 4.6.2 ...... 124 Infl ammatory w ...... 105 4.7 Neoplastic Lesions 4.3.1.1 Radicular Cyst ...... 105 of the Maxillofacial Bones, 4.3.1.2 Paradental Cyst ...... 106 Non-Odontogenic ...... 125 4.3.2 Odontogenic Cysts – 4.7.1 ...... 125 Developmental ...... 106 4.7.2 Chordoma ...... 125 4.3.2.1 ...... 106 4.7.3 Melanotic Neuroectodermal Tumour 4.3.2.2 ...... 107 of Infancy ...... 126 4.3.2.3 Glandular Odontogenic Cyst ...... 107 4.3.2.4 ...... 107 References ...... 126 4.3.2.5 ...... 108 4.3.3 Non-Odontogenic Cysts ...... 109 5 Major and Minor 4.3.3.1 Nasopalatine Duct Cyst ...... 109 Salivary Glands ...... 132 4.3.3.2 ...... 109 S. Di Palma, R.H.W. Simpson, 4.3.3.3 Surgical Ciliated Cyst ...... 109 A. Skalova, I. Leivo 4.3.4 Pseudocysts ...... 109 5.1 Introduction ...... 132 4.3.4.1 Solitary Bone Cyst ...... 109 5.1.1 Normal Salivary Glands ...... 132 4.3.4.2 Focal Bone Marrow Defect ...... 109 5.1.2 Developmental Disorders ...... 132 4.4 Odontogenic Tumours ...... 109 5.2 Obstructive Disorders ...... 132 4.4.1 Odontogenic Tumours – 5.2.1 Mucus Escape Reaction ...... 132 Epithelial ...... 110 5.2.2 Chronic Sclerosing 4.4.1.1 Ameloblastoma ...... 110 of the 4.4.1.2 Calcifying Epithelial (Küttner Tumour) ...... 133 Odontogenic Tumour ...... 112 4.4.1.3 Adenomatoid Odontogenic Tumour . . 112 5.3. Infections ...... 133 4.4.1.4 Squamous Odontogenic Tumour . . . . 113 5.3.1 Bacteria, Fungi ...... 133 4.4.2 Odontogenic Tumours – 5.3.2 Viruses ...... 133 Mesenchymal ...... 114 4.4.2.1 Odontogenic Myxoma ...... 114 5.4 Miscellaneous Infl ammatory 4.4.2.2 Odontogenic Fibroma ...... 115 Disorders ...... 133 4.4.2.3 ...... 116 5.5 Miscellaneous Non-Infl ammatory 4.4.3 Odontogenic Tumours – Disorders ...... 133 Mixed Epithelial and Mesenchymal . . . 117 5.5.1 Necrotising Sialometaplasia 4.4.3.1 Ameloblastic Fibroma ...... 117 (Salivary Gland Infarction) ...... 133 4.4.3.2 Ameloblastic Fibro- ...... 117 5.5.2 Sialadenosis ...... 133 4.4.3.3 Odontoma – Complex Type ...... 118 5.5.3 Adenomatoid Hyperplasia 4.4.3.4 Odontoma – Compound Type ...... 118 of Mucous Salivary Glands ...... 134 4.4.3.5 Odonto-Ameloblastoma ...... 118 5.5.4 Irradiation Changes ...... 134 Contents XV

5.5.5 Tissue Changes 5.9.11.3 Metastasising . . . 157 Following Fine Needle Aspiration . . . . . 134 5.9.12 Sebaceous Carcinoma ...... 158 5.9.13 Lymphoepithelial Carcinoma ...... 158 5.6 Oncocytic Lesions ...... 134 5.9.14 Small Cell Carcinoma ...... 158 5.6.1 Focal and Diff use Oncocytosis ...... 134 5.9.15 Higher Grade Change in Carcinomas . . . 159 5.6.2 Ductal Oncocytosis ...... 134 5.9.16 Metastatic Malignancies ...... 159 5.6.3 Multifocal Nodular Oncocytic Hyperplasia ...... 135 5.10 Hybrid Carcinoma ...... 160 5.7 Cysts ...... 135 5.11 Endodermal Sinus Tumour ...... 160 5.7.1 Salivary Polycystic 5.12 ...... 160 Dysgenetic Disease ...... 135 5.7.2 Mucoceles ...... 135 5.13 Alterations in Gene Expression 5.7.3 Simple Salivary Duct Cysts ...... 135 and Molecular Derangements 5.7.4 Lymphoepithelial Cystic Lesions ...... 135 in Salivary Gland Carcinoma ...... 160 5.7.4.1 Benign Lymphoepithelial Cyst ...... 135 5.13.1 Predominantly 5.7.4.2 Cystic Lymphoid Hyperplasia Myoepithelial Malignancies ...... 161 of AIDS ...... 136 5.13.2 Predominantly 5.7.5 Sclerosing Polycystic Sialadenopathy Epithelial Malignancies ...... 161 (Sclerosing Polycystic Adenosis) ...... 136 5.7.6 Other Cysts ...... 137 5.14 Benign and Malignant Lymphoid Infi ltrates ...... 162 5.8 Benign Tumours ...... 137 5.14.1 Non-Autoimmune 5.8.1 Pleomorphic Adenoma ...... 137 Lymphoid Infi ltrates ...... 162 5.8.1.1 Salivary Gland Anlage Tumour 5.14.2 Benign Autoimmune (“Congenital Pleomorphic Adenoma”) . . 140 Lymphoid Infi ltrates ...... 162 5.8.2 Benign Myoepithelioma ...... 140 5.14.3 Malignant ...... 163 5.8.3 ...... 141 5.15 Other Tumours ...... 163 5.8.4 Warthin’s Tumour ...... 142 5.16 Unclassifi ed Tumours ...... 163 5.8.5 ...... 143 5.8.6 Canalicular Adenoma ...... 143 References ...... 164 5.8.7 Sebaceous Adenoma ...... 144 6 Nasopharynx 5.8.8 Sebaceous Lymphadenoma ...... 144 and Waldeyer’s Ring ...... 171 5.8.9 ...... 144 S. Regauer 5.8.10 Cystadenoma ...... 144 5.9 Malignant Epithelial Tumours ...... 144 6.1 Embryological Development 5.9.1 ...... 144 of the Nasopharynx 5.9.2 ...... 146 and Waldeyer’s Ring ...... 172 5.9.3 ...... 147 6.2 Nasopharynx ...... 173 5.9.4 Polymorphous Low-Grade 6.2.1 Anatomy and Histology ...... 173 Adenocarcinoma ...... 148 6.2.2 Congenital Developmental 5.9.4.1 Cribriform Adenocarcinoma Anomalies ...... 173 of the Tongue ...... 149 6.2.2.1 Nasopharyngeal 5.9.5 Epithelial-Myoepithelial Carcinoma . . . 150 Branchial Cleft Cysts ...... 173 5.9.6 Hyalinising Clear Cell Carcinoma . . . . 151 6.2.2.2 Tornwaldt’s Cyst ...... 173 5.9.7 Basal Cell Adenocarcinoma ...... 151 6.2.2.3 Rathke’s Cleft Cyst/ 5.9.8 Myoepithelial Carcinoma Ectopic Pituitary Tissue ...... 174 (Malignant Myoepithelioma) ...... 152 6.2.2.4 Craniopharyngioma ...... 174 5.9.9 Salivary Duct Carcinoma ...... 154 6.2.2.5 Heterotopic Brain Tissue/ 5.9.10 Oncocytic Carcinoma ...... 155 Encephalocele ...... 174 5.9.11 Malignancy in Pleomorphic Adenoma 6.2.3 Congenital Tumours ...... 174 Malignant Mixed Tumour ...... 156 6.2.3.1 Salivary Gland Anlage Tumour ...... 175 5.9.11.1 Carcinoma 6.2.3.2 Hairy Polyp ...... 175 (True Malignant Mixed Tumour) 6.2.3.3 Congenital Nasopharyngeal Ex Pleomorphic Adenoma ...... 156 Teratoma ...... 175 5.9.11.2 Carcinosarcoma 6.2.4 Benign Tumours Ex Pleomorphic Adenoma ...... 157 and Tumour-Like Lesions ...... 175 XVI Contents

6.2.4.1 Nasopharyngeal Angiofi broma ...... 175 7.2 Laryngocele, Cysts, Heterotopia ...... 199 6.2.4.2 Respiratory Epithelial 7.2.1 General Considerations ...... 199 Adenomatoid Hamartoma ...... 178 7.2.2 Laryngocele ...... 199 6.2.4.3 Nasopharyngeal Inverted Papilloma . . . 178 7.2.3 Sacccular Cyst ...... 199 6.2.4.4 Solitary Fibrous Tumour ...... 179 7.2.4 Ductal Cyst ...... 199 6.2.4.5 Paraganglioma ...... 179 7.2.5 Oncocytic Cyst ...... 200 6.2.4.6 Meningioma ...... 179 7.2.6 Zenker’s Hypopharyngeal Diverticle . . . 201 6.2.4.7 Glandular Retention Cysts ...... 179 7.2.7 Aberrant Th yroid Tissue ...... 201 6.2.5 Nasopharyngeal Carcinoma ...... 180 7.2.8 Tracheopathia Osteochondroplastica . . . 202 6.2.5.1 Non-Keratinising Nasopharyngeal 7.3 Infl ammatory Lesions ...... 202 Carcinoma ...... 180 7.3.1 Acute Infections ...... 202 6.2.5.2 Keratinising Nasopharyngeal 7.3.1.1 Epiglottitis ...... 202 Carcinoma ...... 182 7.3.1.2 Laryngotracheobronchitis ...... 202 6.2.6 Nasopharyngeal Adenocarcinoma . . . . . 182 7.3.1.3 Diphtheria ...... 202 6.2.6.1 Salivary Gland-Type Adenocarcinoma 7.3.2 Chronic Infections ...... 202 of the Nasopharynx ...... 182 7.3.2.1 Tuberculosis ...... 202 6.2.6.2 Papillary Adenocarcinoma 7.3.2.2 Fungal Infections ...... 203 of the Nasopharynx ...... 182 7.3.2.3 Other Rare Infections ...... 203 6.2.7 Malignant Non-Epithelial Tumours 7.3.3 Non-Infectious Infl ammatory of the Nasopharynx ...... 183 Lesions ...... 203 6.2.7.1 Chordoma ...... 183 7.3.3.1 Wegener’s Granulomatosis ...... 203 6.2.7.2 Sarcoma ...... 183 7.3.3.2 Sarcoidosis ...... 204 6.3 Waldeyer’s Ring ...... 183 7.3.3.3 Rheumatoid Arthritis ...... 204 6.3.1 Anatomy and Histology 7.3.3.4 Relapsing Polychondritis ...... 205 of Waldeyer’s Ring ...... 183 7.3.3.5 Gout ...... 206 6.3.2 Congenital Anomalies 7.3.3.6 Tefl on Granuloma ...... 206 of Waldeyer’s Ring ...... 184 7.3.3.7 Idiopathic Subglottic 6.3.3 Tonsillitis ...... 184 Laryngeal Stenosis ...... 206 6.3.3.1 Bacterial Tonsillitis ...... 184 7.3.3.8 Angioneurotic Oedema ...... 207 6.3.3.2 Viral Tonsillitis ...... 185 7.4 Degenerative Lesions ...... 207 6.3.4 Benign Tumours 7.4.1 Oculopharyngeal of Waldeyer’s Ring ...... 187 Muscular Dystrophy ...... 207 6.3.4.1 Squamous Papilloma ...... 187 7.5 Pseudotumours ...... 207 6.3.4.2 Lymphangiomatous Tonsillar Polyp . . . . 187 7.5.1 Exudative Lesions of Reinke’s Space . . . . 207 6.3.5 Carcinomas 7.5.1.1 Reinke’s Oedema ...... 208 of Waldeyer’s Ring ...... 187 7.5.1.2 Vocal Cord Polyp and Nodule ...... 208 6.3.6 Malignant Lymphomas 7.5.2 Contact Ulcer and Granuloma, of Waldeyer’s Ring ...... 189 Intubation Granuloma ...... 210 6.3.6.1 Mantle Cell Lymphoma ...... 189 7.5.3 Necrotising Sialometaplasia ...... 211 6.3.6.2 Extranodal Marginal Zone B-Cell 7.5.4 Metaplastic Elastic Cartilaginous Lymphoma of Mucosa-Associated Nodules ...... 211 Lymphoid Tissue ...... 190 7.5.5 Amyloidosis ...... 211 6.3.6.3 Extranodal NK/T-Cell Lymphoma, 7.5.6 Sinus Histiocytosis Nasal Type ...... 190 with Massive Lymphadenopathy 6.3.6.4 Hodgkin’s Lymphoma ...... 190 and Other Rare Pseudotumours ...... 212 6.3.6.5 Extramedullary Plasmacytoma ...... 190 7.5.7 Infl ammatory Myofi broblastic 6.3.7 Systemic Disease Tumour ...... 213 Aff ecting Waldeyer’s Ring ...... 190 7.6 Benign Neoplasms ...... 214 References ...... 191 7.6.1 Squamous Cell Papilloma ...... 214 7.6.2 Salivary Gland-Type Tumours ...... 214 7 Larynx and Hypopharynx ...... 196 N. Gale, A. Cardesa, N. Zidar 7.6.2.1 Pleomorphic Adenoma ...... 214 7.6.2.2 Oncocytoma ...... 214 7.1 Summary of Anatomy, 7.6.3 Haemangioma Histology and Embryology ...... 198 (Neonatal and Adult Types) ...... 214 Contents XVII

7.6.4 Paraganglioma ...... 215 8.2.2.2 First Branchial Cleft Cyst ...... 238 7.6.5 Granular Cell Tumour ...... 216 8.2.3 Tumour-Like Lesions ...... 239 7.6.6 Chondroma ...... 217 8.2.3.1 Chondrodermatitis Nodularis Helicis . . . 239 8.2.3.2 Keratosis Obturans and Cholesteatoma 7.7 Malignant Neoplasms ...... 217 of External Canal ...... 239 7.7.1 Potentially Malignant (Precancerous) 8.2.3.3 Keratin Granuloma ...... 239 Lesions ...... 217 8.2.3.4 Angiolymphoid Hyperplasia 7.7.2 Invasive Squamous Cell Carcinoma . . . . 218 with Eosinophilia 7.7.2.1 Epidemiology ...... 218 and Kimura’s Disease ...... 239 7.7.2.2 Aetiology ...... 218 8.2.3.5 Accessory Tragus ...... 240 7.7.2.3 Anatomic Sites ...... 218 8.2.3.6 Keloid ...... 240 7.7.2.4 Histological Variants ...... 219 8.2.4 Benign Neoplasms ...... 240 7.7.2.5 TNM Grading ...... 220 8.2.4.1 Adenoma of Ceruminal Glands ...... 240 7.7.3 Neuroendocrine Carcinoma ...... 220 8.2.4.2 Pleomorphic Adenoma 7.7.3.1 Well-Diff erentiated of Ceruminal Glands ...... 241 Neuroendocrine Carcinoma 8.2.4.3 Syringocystadenoma Papilliferum (Carcinoid) ...... 220 of Ceruminal Glands ...... 241 7.7.3.2 Moderately Diff erentiated 8.2.4.4 Bony Lesions ...... 241 Neuroendocrine Carcinoma 8.2.5 Malignant Neoplasms ...... 242 (Atypical Carcinoid) ...... 220 8.2.5.1 Adenocarcinoma 7.7.3.3 Poorly Diff erentiated of Ceruminal Glands ...... 242 Neuroendocrine Carcinoma 8.2.5.2 Adenoid Cystic Carcinoma (Small Cell Carcinoma) ...... 221 of Ceruminal Glands ...... 242 7.7.4 Adenocarcinoma ...... 222 8.2.5.3 Basal Cell Carcinoma ...... 242 7.7.4.1 Adenoid Cystic Carcinoma ...... 222 8.2.5.4 Squamous Cell Carcinoma ...... 243 7.7.4.2 Mucoepidermoid Carcinoma ...... 222 8.2.5.5 Melanotic Neoplasms ...... 243 7.7.5 Sarcomas ...... 223 7.7.5.1 Chondrosarcoma ...... 223 8.3 Middle Ear and Mastoid ...... 244 7.7.5.2 Other Sarcomas ...... 224 8.3.1 Infl ammatory Lesions ...... 244 7.7.6 Other Malignant Neoplasms ...... 224 8.3.1.1 Acute and Chronic Otitis Media ...... 244 7.7.6.1 Malignant Lymphoma ...... 224 8.3.1.2 Cholesteatoma ...... 244 7.7.6.2 Extraosseus (Extramedullary) 8.3.1.3 Unusual Infl ammatory Lesions ...... 247 Plasmacytoma ...... 224 8.3.2 Neoplasms and Lesions 7.7.6.3 Primary ...... 225 Resembling Neoplasms ...... 247 7.7.6.4 Metastases to the Larynx ...... 225 8.3.2.1 Choristoma (Salivary Gland, Glial References ...... 226 and Sebaceous Types) ...... 247 8.3.2.2 Adenoma ...... 247 8 Ear and Temporal Bone ...... 234 L. Michaels 8.3.2.3 Papillary Tumours ...... 248 8.3.2.4 Jugulotympanic Paraganglioma ...... 249 8.1 Summary of Embryology, 8.3.2.5 Squamous Carcinoma ...... 250 Anatomy and Histology ...... 236 8.3.2.6 Meningioma ...... 251 8.1.1 Embryology ...... 236 8.3.2.7 Rhabdomyosarcoma ...... 251 8.1.2 Anatomy ...... 236 8.3.2.8 Metastatic Carcinoma ...... 252 8.1.3 Histology ...... 237 8.4 Inner Ear ...... 252 8.2 External Ear and Auditory Canal . . . . . 237 8.4.1 Bony Labyrinth ...... 252 8.2.1 Infl ammatory and Metabolic Lesions . . . 237 8.4.1.1 Otosclerosis ...... 252 8.2.1.1 Diff use External Otitis ...... 237 8.4.1.2 Paget’s Disease ...... 253 8.2.1.2 Perichondritis ...... 237 8.4.1.3 Osteogenesis Imperfecta ...... 254 8.2.1.3 Malignant Otitis Externa ...... 237 8.4.1.4 Osteopetrosis ...... 254 8.2.1.4 Relapsing Polychondritis ...... 238 8.4.2 Membranous Labyrinth 8.2.1.5 Gout ...... 238 and Cranial Nerves ...... 254 8.2.1.6 Ochronosis ...... 238 8.4.2.1 Viral, Bacterial 8.2.2 Pseudocystic and Cystic Lesions ...... 238 and Mycotic Infections ...... 254 8.2.2.1 Idiopathic Pseudocystic 8.4.2.2 Lesions of the Vestibular System ...... 256 Chondromalacia ...... 238 8.4.2.3 Tumours and Tumour-Like Lesions . . . . 257 XVIII Contents

8.4.2.4 Presbyacusis ...... 260 9.7.3 Histologic Evaluation 8.4.2.5 Malformations ...... 260 of Neck Dissection ...... 279 References ...... 260 References ...... 280

9 Cysts and Unknown Primary 10 Eye and Ocular Adnexa ...... 282 and Secondary Tumours of the Neck, M.R. Canninga-Van Dijk and Neck Dissection ...... 262 M. A Luna, K. Pineda-Daboin 10.1 Summary of Anatomy and Histology ...... 284 9.1 Introduction ...... 264 10.1.1 Conjunctiva ...... 284 10.1.2 Cornea ...... 284 9.2. Anatomy ...... 264 10.1.3 Intraocular Tissues ...... 284 9.2.1 Triangles of the Neck ...... 264 10.1.4 Optic Nerve ...... 284 9.2.2 Lymph Node Regions 10.1.5 Lacrimal Glands of the Neck ...... 264 and Lacrimal Passages ...... 284 9.3 Cysts of the Neck ...... 264 10.1.6 Eyelids ...... 284 9.3.1 Developmental Cysts ...... 265 10.1.7 Orbit ...... 285 9.3.1.1 Branchial Cleft Cysts, 10.2 Conjunctiva ...... 285 Sinuses and Fistulae ...... 265 10.2.1 Developmental Anomalies ...... 285 9.3.2 Branchiogenic Carcinoma ...... 267 10.2.1.1 Dermoid, Dermolipoma 9.3.3 Th yroglossal Duct Cyst and Complex Choristoma ...... 285 and Ectopic Th yroid ...... 268 10.2.2 Cysts ...... 285 9.3.4 Cervical Th ymic Cyst ...... 269 10.2.2.1 Inclusion cysts ...... 285 9.3.5 Cervical Parathyroid Cyst ...... 270 10.2.3 Degeneration ...... 286 9.3.6 Cervical Bronchogenic Cyst ...... 270 10.2.3.1 Pinguecula and Pterygium ...... 286 9.3.7 Dermoid Cyst ...... 271 10.2.4 Infl ammatory Processes ...... 286 9.3.8 Unclassifi ed Cervical Cyst ...... 271 10.2.4.1 Acute Conjunctivitis ...... 286 9.3.9 Non-Developmental Cysts ...... 271 10.2.4.2 Chronic Non-Granulomatous 9.3.9.1 ...... 271 Conjunctivitis ...... 287 9.3.9.2 Laryngocele ...... 271 10.2.4.3 Granulomatous Conjunctivitis ...... 287 9.4 Cystic Neoplasms ...... 272 10.2.4.4 Ligneous Conjunctivitis ...... 287 9.4.1 10.2.4.5 Chlamydia Trachomatis (TRIC Agent) and Lymphangioma ...... 272 Infection ...... 287 9.4.2 Haemangioma ...... 272 10.2.5 Dermatologic 9.4.3 Teratoma ...... 272 and Systemic Diseases ...... 288 9.4.4 Cervical Salivary 10.2.5.1 Keratoconjunctivitis Sicca ...... 288 Gland Cystic Neoplasms ...... 273 10.2.5.2 Dermatologic Diseases ...... 288 9.4.5 Miscellaneous Lesions ...... 273 10.2.5.3 Metabolic Diseases ...... 288 10.2.6 Tumours 9.5 Paraganglioma ...... 273 and Tumour-Like Conditions ...... 288 9.6 Unknown Primary 10.2.6.1 Epithelial ...... 288 and Secondary Tumours ...... 274 10.2.6.2 Melanocytic ...... 290 9.6.1 Defi nition ...... 274 10.2.6.3 Other Neoplasms ...... 291 9.6.2 Clinical Features ...... 275 10.3 Cornea ...... 292 9.6.3 Search for the Primary Tumour ...... 275 10.3.1 Keratitis and Corneal Ulcers ...... 292 9.6.4 Common Location 10.3.1.1 Herpes Simplex Keratitis ...... 292 of the Primary Tumour ...... 276 10.3.1.2 Corneal Ulceration 9.6.5 Histologic Type of Metastases Due to Systemic Disease ...... 292 and Immunohistochemical Features . . . 276 10.3.2 Keratoconus ...... 292 9.6.6 Diff erential Diagnosis ...... 276 10.3.3 Hereditary Corneal Dystrophies . . . . . 293 9.6.7 Treatment and Results ...... 278 10.3.3.1 Epithelial Dystrophies ...... 293 9.7 Neck Dissection ...... 278 10.3.3.2 Stromal Dystrophies ...... 293 9.7.1 Classifi cation of Neck Dissections . . . . . 278 10.3.3.3 Endothelial Dystrophies ...... 293 9.7.2 Gross Examination 10.3.4 Failed Previous Graft s ...... 294 of Neck Dissection Surgical Specimens . . 279 Contents XIX

10.4 Intraocular Tissues ...... 294 10.5.4 Tumours ...... 302 10.4.1 Developmental Anomalies ...... 294 10.5.4.1 Glioma ...... 302 10.4.1.1 Congenital Glaucoma ...... 294 10.5.4.2 Meningioma ...... 302 10.4.1.2 Retinopathy of Prematurity ...... 294 10.6 Lacrimal Gland 10.4.1.3 Persistent Primary Hyperplastic and Lacrimal Passages ...... 302 Vitreous ...... 294 10.6.1 Infl ammatory Processes ...... 302 10.4.1.4 Retinal Dysplasia ...... 294 10.6.2 Tumours 10.4.1.5 Aniridia ...... 294 and Tumour-Like Conditions ...... 303 10.4.1.6 Congenital Rubella Syndrome ...... 294 10.4.2 Infl ammatory Processes ...... 295 10.7 Eyelids ...... 303 10.4.2.1 Acute Infl ammation ...... 295 10.7.1 Cysts ...... 303 10.4.2.2 Chronic Non-Granulomatous 10.7.1.1 Dermoid Cyst ...... 303 Infl ammation ...... 295 10.7.1.2 Epidermal Cyst ...... 303 10.4.2.3 Granulomatous Infl ammation ...... 295 10.7.1.3 Hidrocystoma ...... 303 10.4.3 Trauma ...... 296 10.7.2 Infl ammatory Processes ...... 303 10.4.4 Degeneration ...... 296 10.7.2.1 Chalazion and Other Ruptured Cysts . . . 304 10.4.4.1 Glaucoma ...... 296 10.7.2.2 Deep Granuloma Annulare ...... 304 10.4.4.2 Cataracts ...... 297 10.7.2.3 Necrobiotic Xanthogranuloma ...... 304 10.4.4.3 Phtisis Bulbi ...... 298 10.7.3 Amyloidosis ...... 305 10.4.4.4 Retinal Vascular Disease ...... 298 10.7.4 Tumours 10.4.4.5 Retinal Detachment ...... 298 and Tumour-Like Conditions ...... 305 10.4.4.6 Retinitis Pigmentosa ...... 298 10.7.4.1 Xanthelasmata ...... 305 10.4.5 Tumours and Tumour-Like Conditions ...... 298 10.8 Orbit ...... 305 10.4.5.1 Melanocytic ...... 298 10.8.1 Infl ammatory Processes ...... 305 10.4.5.2 Lymphoid ...... 300 10.8.1.1 Dysthyroid Ophthalmopathy ...... 305 10.4.5.3 Retinoblastoma 10.8.1.2 Cellulitis ...... 305 and Pseudoretinoblastoma ...... 300 10.8.1.3 Pseudotumour ...... 306 10.4.5.4 Glial ...... 301 10.8.2 Tumours 10.4.5.5 Vascular ...... 301 and Tumour-Like Conditions ...... 306 10.4.5.6 Other Primary Tumours ...... 301 10.8.2.1 Developmental Cysts ...... 306 10.4.5.7 Metastatic Tumours ...... 302 10.8.2.2 Optic Nerve and Meningeal Tumours ...... 306 10.5 Optic Nerve ...... 302 10.8.2.3 Metastatic Tumours ...... 307 10.5.1 Papilloedema ...... 302 10.5.2 Optic Neuritis ...... 302 References ...... 307 10.5.3 Optic Atrophy ...... 302 Subject Index ...... 311 List of Contributors

Llucia Alos Ilmo Leivo (e-mail: [email protected]) (e-mail: [email protected]) Department of Pathological Anatomy, Department of Pathology, Haartman Institute, Hospital Clinic, University of Barcelona, P.O. Box 21 (Haartmaninkatu 3) Villarroel 170, 08036 Barcelona, Spain 00014 University of Helsinki, Helsinki, Finland

M.R. Canninga-Van Dijk Mario A. Luna (e-mail: [email protected]) (e-mail: [email protected]) Department of Pathology, Department of Pathology, The University of Texas, University Medical Centre Utrecht, H04-312, M.D. Anderson Cancer Center, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands 1515 Holcombe Blvd, Box 85, Houston, Texas 77030, USA Antonio Cardesa (e-mail: [email protected]) Leslie Michaels Department of Pathological Anatomy, (e-mail: [email protected]) Hospital Clinic, University of Barcelona, Department of Histopathology, Villarroel 170, 08036 Barcelona, Spain Royal Free and UCL Medical School, Rockefeller Building, Silvana Di Palma University Street, London WC1E 6JJ, UK (e-mail: [email protected]) Department of Histopathology, Keyla Pineda-Daboin University of Surrey, Royal Surrey County Hospital, Department of Pathology, Egerton Road, Guildford, GU2 7XX, UK Military Hospital “Carlos Arvelo” and Institute of Anatomical Pathology, John Wallace Eveson University Central of Venezuela, Caracas, Venezuela (e-mail: [email protected]) Division of , Sigrid Regauer Pathology and Microbiology, (e-mail: [email protected]) University of Bristol Dental School, Institute of Pathology, Lower Maudlin Street, Bristol, BS1 2LY, UK Karl Franzens University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria Alessandro Franchi (e-mail: [email protected]) Roderick H.W. Simpson Department of Human Pathology and Oncology, (e-mail: [email protected]) University of Florence, Department of Histopathology, Viale Morgagni 85, 50134 Florence, Italy Church Lane Exeter, EX2 5AD, UK

Nina Gale Alena Skalova (e-mail: [email protected]) (e-mail: [email protected]) Institute of Pathology, Faculty of Medicine, Department of Pathology, University of Ljubljana, Medical Faculty Hospital, Korytkova 2, 1000 Ljubljana, Slovenia Dr. E Benese 13, 305 99 Plzen, Czech Republic XXII List of Contributors

Pieter J. Slootweg Nina Zidar (e-mail: [email protected]) (e-mail: [email protected]) Department of Pathology, Institute of Pathology, Faculty of Medicine, University Medical Center St. Radboud, HP 437, University of Ljubljana, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Korytkova 2, 1000 Ljubljana, Slovenia